Publications by authors named "James F Meschia"

281 Publications

Genetics, Genomics, and Precision Medicine.

Stroke 2021 Sep 2:STROKEAHA121033966. Epub 2021 Sep 2.

Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Germany (M.D.).

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http://dx.doi.org/10.1161/STROKEAHA.121.033966DOI Listing
September 2021

Baseline Cognitive Impairment in Patients With Asymptomatic Carotid Stenosis in the CREST-2 Trial.

Stroke 2021 Aug 26:STROKEAHA120032972. Epub 2021 Aug 26.

Department of Biostatistics, University of Alabama School of Public Health (G.H.).

Background And Purpose: Studies of carotid artery disease have suggested that high-grade stenosis can affect cognition, even without stroke. The presence and degree of cognitive impairment in such patients have not been reported and compared with a demographically matched population-based cohort.

Methods: We studied cognition in 1000 consecutive CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) patients, a treatment trial for asymptomatic carotid disease. Cognitive assessment was after randomization but before assigned treatment. The cognitive battery was developed in the general population REGARDS Study (Reasons for Geographic and Racial Differences in Stroke), involving Word List Learning Sum, Word List Recall, and Word List fluency for animal names and the letter F. The carotid stenosis patients were >45 years old with ≥70% asymptomatic carotid stenosis and no history of prevalent stroke. The distribution of cognitive performance for the patients was standardized, accounting for age, race, and education using performance from REGARDS, and after further adjustment for hypertension, diabetes, dyslipidemia, and smoking. Using the Wald Test, we tabulated the proportion of scores less than the anticipated deviate for the population-based cohort for representative percentiles.

Results: There were 786 baseline assessments. Mean age was 70 years, 58% men, and 52% right-sided stenosis. The overall score for patients was significantly below expected for higher percentiles (<0.0001 for 50th, 75th, and 95th percentiles) and marginally below expected for the 25th percentile (=0.015). Lower performance was attributed largely to Word List Recall (<0.0001 for all percentiles) and for Word List Learning (50th, 75th, and 95th percentiles below expected, ≤0.01). The scores for left versus right carotid disease were similar.

Conclusions: Baseline cognition of patients with severe carotid stenosis showed below normal cognition compared to the population-based cohort, controlling for demographic and cardiovascular risk factors. This cohort represents the largest group to date to demonstrate that poorer cognition, especially memory, in this disease.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02089217.
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http://dx.doi.org/10.1161/STROKEAHA.120.032972DOI Listing
August 2021

Safety of the transradial approach to carotid stenting.

Catheter Cardiovasc Interv 2021 Aug 13. Epub 2021 Aug 13.

Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.

Background: The multicenter prospective CREST-2 Registry (C2R) provides recent experience in performing carotid artery stenting (CAS) for interventionists to ensure safe performance of CAS.

Objective: To determine the periprocedural safety of CAS performed using a transradial approach relative to CAS performed using a transfemoral approach.

Methods: Patients with ≥70% asymptomatic and ≥50% symptomatic carotid stenosis, ≤80 years of age and at standard or high risk for carotid endarterectomy (CEA) are eligible for the C2R. The primary endpoint was a composite of severe access-related complications. Comparisons were made using propensity-score matched logistic regression.

Results: The mean age of the cohort was 67.6 ± 8.2 years and 1906 (35.1%) were female. Indications for CAS included 4063 (74.9%) for primary atherosclerosis. A total of 2868 (52.8%) cases underwent CAS for asymptomatic disease. Transradial access was used in 213 (3.9%) patients. The transradial cohort had lower use of general anesthesia (1.5% vs. 6.3%, p = 0.007) and higher use of distal embolic protection (96.7% vs. 89.4%, p = 0.0004). There were no significant differences between radial and femoral access groups in terms of a composite of major access-related complications (0% vs. 1.1%) or a composite of periprocedural stroke or death (3.3% vs. 2.4%; OR = 1.4 [confidence intervals 0.6, 3.1]; p = 0.42).

Conclusion: We found no significant differences in rates of major access-related complications or periprocedural stroke or death with CAS performed using transradial compared to transfemoral access. Our results support incorporation of the transradial approach to clinical trials comparing CAS to other revascularization techniques.
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http://dx.doi.org/10.1002/ccd.29912DOI Listing
August 2021

MRI Radiomic Signature of White Matter Hyperintensities Is Associated With Clinical Phenotypes.

Front Neurosci 2021 12;15:691244. Epub 2021 Jul 12.

Department of Neurology, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, MO, United States.

Objective: Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes.

Methods: We analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask-WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with stable selected features predictive of WMH burden and then related this signature to clinical variables using canonical correlation analysis (CCA).

Results: Radiomic features were predictive of WMH burden ( = 0.855 ± 0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected -values < 0.001, -value = 0.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and diabetes, CV4 by hypertension, CV5 by atrial fibrillation (AF) and diabetes, CV6 by coronary artery disease (CAD), and CV7 by CAD and diabetes.

Conclusion: Radiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes, suggesting different radiographical textural abnormalities per cardiovascular risk profile. Further research could evaluate radiomics to predict the progression of WMH and for the follow-up of stroke patients' brain health.
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http://dx.doi.org/10.3389/fnins.2021.691244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312571PMC
July 2021

Outcomes and Surgical Considerations for Neurosurgical Patients Hospitalized with COVID-19-A Multicenter Case Series.

World Neurosurg 2021 Jul 6. Epub 2021 Jul 6.

Department of Neurological Surgery, Mayo Clinic, Jacksonville, Florida. Electronic address:

Objective: Neurosurgical patients are at a higher risk of having a severe course of coronavirus disease 2019 (COVID-19). The objective of this study was to determine morbidity, hospital course, and mortality of neurosurgical patients during the coronavirus disease 2019 (COVID-19) pandemic in a multicenter health care system.

Methods: A retrospective observational study was conducted to identify all hospitalized neurosurgical patients positive for COVID-19 from March 11, 2020 to November 2, 2020 at Mayo Clinic and the Mayo Clinic Health System.

Results: Eleven hospitalized neurosurgical patients (0.68%) were positive for COVID-19. Four patients (36.6%) were men and 7 (63.3%) were women. The mean age was 65.7 years (range, 35-81 years). All patients had comorbidities. The mean length of stay was 13.4 days (range, 4-30 days). Seven patients had a central nervous system malignancy (4 metastases, 1 meningioma, 1 glioblastoma, and 1 schwannoma). Three patients presented with cerebrovascular complications, comprising 2 spontaneous intraparenchymal hemorrhages and 1 ischemic large-vessel stroke. One patient presented with an unstable traumatic spinal burst fracture. Four patients underwent neurosurgical/neuroendovascular interventions. Discharge disposition was to home in 5 patients, rehabilitation facility in 3, and hospice in 3. Five patients had died at follow-up, 3 within 30 days from COVID-19 complications and 2 from progression of their metastatic cancer.

Conclusions: COVID-19 is rare among the inpatient neurosurgical population. In all cases, patients had multiple comorbidities. All symptomatic patients from the respiratory standpoint had complications during their hospitalization. Deaths of 3 patients who died within 30 days of hospitalization were all related to COVID-19 complications. Neurosurgical procedures were performed only if deemed emergent.
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http://dx.doi.org/10.1016/j.wneu.2021.06.147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257398PMC
July 2021

NIH funding trends for neurosurgeon-scientists from 1993-2017: Biomedical workforce implications for neurooncology.

J Neurooncol 2021 Aug 7;154(1):51-62. Epub 2021 Jul 7.

Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, USA.

Introduction: Neurosurgeons represent 0.5% of all physicians and currently face a high burden of disease. Physician-scientists are essential to advance the mission of National Academies of Science (NAS) and National Institutes of Health (NIH) through discovery and bench to bedside translation. We investigated trends in NIH neurosurgeon-scientist funding over time as an indicator of physician-scientist workforce training.

Methods: We used NIH Research Portfolio Online Reporting Tools (RePORTER) to extract grants to neurosurgery departments and neurosurgeons from 1993 to 2017. Manual extraction of each individual grant awardee was conducted.

Results: After adjusting for U.S. inflation (base year: 1993), NIH funding to neurosurgery departments increased yearly (P < 0.00001). However, neurosurgeon-scientists received significantly less NIH funding compared to scientists (including basic scientists and research only neurosurgeons) (P = 0.09). The ratio of neurosurgeon-scientists to scientists receiving grants was significantly reduced (P = 0.002). Interestingly, the percentage of oncology-related neurosurgery grants significantly increased throughout the study period (P = 0.002). The average number of grants per neurosurgeon-scientists showed an upward trend (P < 0.001); however, the average number of grants for early-career neurosurgeon-scientists, showed a significant downward trend (P = 0.05).

Conclusion: Over the past 23 years, despite the overall increasing trends in the number of NIH grants awarded to neurosurgery departments overall, the proportion of neurosurgeon-scientists that were awarded NIH grants compared to scientists demonstrates a declining trend. This observed shift is disproportionate in the number of NIH grants awarded to senior level compared to early-career neurosurgeon-scientists, with more funding allocated towards neurosurgical-oncology-related grants.
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http://dx.doi.org/10.1007/s11060-021-03797-5DOI Listing
August 2021

Yield of Head Imaging in Ambulatory and Hospitalized Patients With SARS-CoV-2: A Multi-Center Study of 8675 Patients.

Neurohospitalist 2021 Jul 16;11(3):221-228. Epub 2020 Dec 16.

Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.

Background And Purpose: To describe the neurological and cerebrovascular findings in patients who tested positive for SARS-CoV-2 and underwent head imaging in ambulatory and inpatient settings.

Methods: Consecutive patients aged ≥18 years with SARS-CoV-2 infection diagnosed or treated at Mayo Clinic sites from 3/11/2020 to 7/23/2020 with head CT or brain MRI within 30 days of SARS-CoV-2 diagnosis were included. Demographics, medical history, indication for SARS-CoV-2 testing, neurologic symptoms, indication for brain imaging, neuroimaging findings, etiology of cerebrovascular events, and hospital course were abstracted from medical records.

Results: Of 8,675 patients with SARS-CoV-2, 180 (2.07%) had head imaging. Mean age of the entire cohort was 42 ± 18 years, whereas mean age of those with head imaging was 62 ± 19 years. Common indications for imaging were headache (34.4%), encephalopathy (33.4%), focal neurologic symptom (16.7%), and trauma (13.9%). While 86.1% of patients who underwent head imaging had normal exams, cerebrovascular events occurred in 18 patients (0.21% of the total cohort). Of patients with cerebrovascular events, 8 (44.5%) had acute infarct; 6 (33.3%), acute intracranial hemorrhage; 5 (2.8%), subacute infarct; and 1 (0.6%) posterior reversible encephalopathy syndrome. In the thirteen patients with ischemic stroke, 6 (46.2%) had cryptogenic stroke; 3 (23.1%), other defined causes; 2 (15.4%), small vessel stroke; 1 (7.7%), large vessel stroke; and 1 (7.7%) cardioembolic stroke.

Conclusion: In ambulatory and hospitalized patients with SARS-CoV-2 infection, the rate of head imaging is low, with common indications of encephalopathy and headache. Cerebrovascular events occurred rarely, and cryptogenic stroke was the most common stroke mechanism.
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http://dx.doi.org/10.1177/1941874420980622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746954PMC
July 2021

Non-Adherence to Antihypertensive Guidelines in Patients with Asymptomatic Carotid Stenosis.

J Stroke Cerebrovasc Dis 2021 Aug 18;30(8):105918. Epub 2021 Jun 18.

Department of Neurology, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL 32224, United States. Electronic address:

Importance: Hypertension and carotid stenosis are both risk factors for stroke, but the presence of carotid stenosis might dampen enthusiasm for tight control of hypertension because of concerns for hypoperfusion.

Objective: To determine the extent to which there are opportunities to potentially improve pharmacotherapy for hypertension in patients known to have asymptomatic high-grade carotid stenosis.

Design: We examined anti-hypertensive medication prescription and adherence to evidence-based hypertension treatment guidelines in a cross-sectional analysis of baseline data of patients enrolled in a clinical trial.

Setting: The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) is a multicenter prospective randomized open blinded end-point clinical trial of intensive medical management with or without revascularization by endarterectomy or stenting for asymptomatic high-grade carotid stenosis.

Participants: 1479 participants (38.6% female; mean age 69.8 years) from 132 clinical centers enrolled in the CREST-2 trial as of April 6, 2020 who were taking ≥1 antihypertensive drug at baseline.

Exposures: Pharmacotherapy for hypertension.

Main Outcome: Adherence to evidence-based guidelines for treating hypertension.

Results: Of 1458 participants with complete data, 26% were on one, 31% on 2, and 43% on ≥3 antihypertensive medications at trial entry. Thirty-two percent of participants were prescribed thiazide; 74%, angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB); 38%, calcium channel blocker (CCB); 56%, a beta blocker; 11%, loop diuretic; and 27%, other. Of those prescribed a single antihypertensive medication, the proportion prescribed thiazide was 5%; ACEI or ARB, 55%, and CCB, 11%. The prevalence of guideline-adherent regimens was 34% (95% CI, 31-36%).

Conclusions And Relevance: In a diverse cohort with severe carotid disease and hypertension, non-adherence to hypertension guidelines was common. All preferred classes of antihypertensive drug were under-prescribed. Using staged iterative guideline-based care for hypertension, CREST-2 will characterize drug tolerance and stroke rates under these conditions.

Trial Registration: ClinicalTrials.gov Number NCT02089217.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105918DOI Listing
August 2021

Serum neurofilament light protein correlates with unfavorable clinical outcomes in hospitalized patients with COVID-19.

Sci Transl Med 2021 07 15;13(602). Epub 2021 Jun 15.

Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

Brain imaging studies of patients with COVID-19 show evidence of macro- and microhemorrhagic lesions, multifocal white matter hyperintensities, and lesions consistent with posterior reversible leukoencephalopathy. Imaging studies, however, are subject to selection bias, and prospective studies are challenging to scale. Here, we evaluated whether serum neurofilament light chain (NFL), a neuroaxonal injury marker, could predict the extent of neuronal damage in a cohort of 142 hospitalized patients with COVID-19. NFL was elevated in the serum of patients with COVID-19 compared to healthy controls, including those without overt neurological manifestations. Higher NFL serum concentrations were associated with worse clinical outcomes. In 100 hospitalized patients with COVID-19 treated with remdesivir, a trend toward lower NFL serum concentrations was observed. These data suggest that patients with COVID-19 may experience neuroaxonal injury and may be at risk for long-term neurological sequelae. Neuroaxonal injury should be considered as an outcome in acute pharmacotherapeutic trials for COVID-19.
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http://dx.doi.org/10.1126/scitranslmed.abi7643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432951PMC
July 2021

Outcome after acute ischemic stroke is linked to sex-specific lesion patterns.

Nat Commun 2021 06 2;12(1):3289. Epub 2021 Jun 2.

Department of Neurology, Washington University School of Medicine & Barnes-Jewish Hospital, St Louis, MO, USA.

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.
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http://dx.doi.org/10.1038/s41467-021-23492-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172535PMC
June 2021

Cognitive Impairment and Dementia After Stroke: Design and Rationale for the DISCOVERY Study.

Stroke 2021 Aug 27;52(8):e499-e516. Epub 2021 May 27.

J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston (N.S.R., S.M.G.).

Stroke is a leading cause of the adult disability epidemic in the United States, with a major contribution from poststroke cognitive impairment and dementia (PSCID), the rates of which are disproportionally high among the health disparity populations. Despite the PSCID's overwhelming impact on public health, a knowledge gap exists with regard to the complex interaction between the acute stroke event and highly prevalent preexisting brain pathology related to cerebrovascular and Alzheimer disease or related dementia. Understanding the factors that modulate PSCID risk in relation to index stroke event is critically important for developing personalized prognostication of PSCID, targeted interventions to prevent it, and for informing future clinical trial design. The DISCOVERY study (Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on Recovery), a collaborative network of thirty clinical performance clinical sites with access to acute stroke populations and the expertise and capacity for systematic assessment of PSCID will address this critical challenge. DISCOVERY is a prospective, multicenter, observational, nested-cohort study of 8000 nondemented ischemic and hemorrhagic stroke patients enrolled at the time of index stroke and followed for a minimum of 2 years, with serial cognitive evaluations and assessments of functional outcome, with subsets undergoing research magnetic resonance imaging and positron emission tomography and comprehensive genetic/genomic and fluid biomarker testing. The overall scientific objective of this study is to elucidate mechanisms of brain resilience and susceptibility to PSCID in diverse US populations based on complex interplay between life-course exposure to multiple vascular risk factors, preexisting burden of microvascular and neurodegenerative pathology, the effect of strategic acute stroke lesions, and the mediating effect of genomic and epigenomic variation.
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http://dx.doi.org/10.1161/STROKEAHA.120.031611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316324PMC
August 2021

Rare Missense Functional Variants at and in Sporadic Intracerebral Hemorrhage.

Neurology 2021 May 24. Epub 2021 May 24.

Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK

ObjectiveTo test the genetic contribution of rare missense variants in and in which common variants are genetically associated with sporadic intracerebral hemorrhage (ICH), we performed rare variant analysis in multiple sequencing data for the risk for sporadic ICH.MethodsWe performed sequencing across 559Kbp at 13q34 including and among 2,133 individuals (1,055 ICH cases; 1,078 controls) in US-based and 1,492 individuals (192 ICH cases; 1,189 controls) from Scotland-based cohorts, followed by sequence annotation, functional impact prediction, genetic association testing, and thermodynamic modeling.ResultsWe identified 107 rare nonsynonymous variants in sporadic ICH, of which two missense variants, rs138269346 (COL4A1) and rs201716258 (COL4A2), were predicted to be highly functional and occurred in multiple ICH cases but not in controls from the US-based cohort. The minor allele of rs201716258 was also present in Scottish ICH patients, and rs138269346 was observed in two ICH-free controls with a history of hypertension and myocardial infarction. Rs138269346 was nominally associated with non-lobar ICH risk (P=0.05), but not with lobar ICH (P=0.08), while associations between rs201716258 and ICH subtypes were non-significant (P>0.12). Both variants were considered pathogenic based on minor allele frequency (<0.00035 in EUR), predicted functional impact ( or ), and modeling studies (substantially altered physical length and thermal stability of collagen).ConclusionsWe identified rare missense variants in / in association with sporadic ICH. Our annotation and simulation studies suggest that these variants are highly functional and may represent targets for translational follow-up.
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http://dx.doi.org/10.1212/WNL.0000000000012227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302151PMC
May 2021

Deep vein thrombosis and pulmonary embolism among hospitalized coronavirus disease 2019-positive patients predicted for higher mortality and prolonged intensive care unit and hospital stays in a multisite healthcare system.

J Vasc Surg Venous Lymphat Disord 2021 Apr 6. Epub 2021 Apr 6.

Division of Vascular Medicine of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn.

Objective: We assessed the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients with coronavirus disease 2019 (COVID-19) compared with that in a matched cohort with similar cardiovascular risk factors and the effects of DVT and PE on the hospital course.

Methods: We performed a retrospective review of prospectively collected data from COVID-19 patients who had been hospitalized from March 11, 2020 to September 4, 2020. The patients were randomly matched in a 1:1 ratio by age, sex, hospital of admission, smoking history, diabetes mellitus, and coronary artery disease with a cohort of patients without COVID-19. The primary endpoint was the incidence of DVT/PE and the odds of developing DVT/PE using a conditional logistic regression model. The secondary endpoint was the hospitalization outcomes for COVID-19 patients with and without DVT/PE, including mortality, intensive care unit (ICU) admission, ICU stay, and length of hospitalization (LOH). Multivariable regression analysis was performed to identify the variables associated with mortality, ICU admission, discharge disposition, ICU duration, and LOH.

Results: A total of 13,310 patients had tested positive for COVID-19, 915 of whom (6.9%) had been hospitalized across our multisite health care system. The mean age of the hospitalized patients was 60.8 ± 17.0 years, and 396 (43.3%) were women. Of the 915 patients, 82 (9.0%) had had a diagnosis of DVT/PE confirmed by ultrasound examination of the extremities and/or computed tomography angiography of the chest. The odds of presenting with DVT/PE in the setting of COVID-19 infection was greater than that without COVID-19 infection (0.6% [5 of 915] vs 9.0% [82 of 915]; odds ratio [OR], 18; 95% confidence interval [CI], 8.0-51.2; P < .001). The vascular risk factors were not different between the COVID-19 patients with and without DVT/PE. Mortality (P = .02), the need for ICU stay (P < .001), duration of ICU stay (P < .001), and LOH (P < .001) were greater in the DVT/PE cohort than in the cohort without DVT/PE. On multivariable logistic regression analysis, the hemoglobin (OR, 0.71; 95% CI, 0.46-0.95; P = .04) and D-dimer (OR, 1.0; 95% CI, 0.33-1.56; P = .03) levels were associated with higher mortality. Higher activated partial thromboplastin times (OR, 1.1; 95% CI, 1.00-1.12; P = .03) and higher interleukin-6 (IL-6) levels (OR, 1.0; 95% CI, 1.01-1.07; P = .05) were associated with a greater risk of ICU admission. IL-6 (OR, 1.0; 95% CI, 1.00-1.02; P = .05) was associated with a greater risk of rehabilitation placement after discharge. On multivariable gamma regression analysis, hemoglobin (coefficient, -3.0; 95% CI, 0.03-0.08; P = .005) was associated with a prolonged ICU stay, and the activated partial thromboplastin time (coefficient, 2.0; 95% CI, 0.003-0.006; P = .05), international normalized ratio (coefficient, -3.2; 95% CI, 0.06-0.19; P = .002) and IL-6 (coefficient, 2.4; 95% CI, 0.0011-0.0027; P = .02) were associated with a prolonged LOH.

Conclusions: A significantly greater incidence of DVT/PE occurred in hospitalized COVID-19-positive patients compared with a non-COVID-19 cohort matched for cardiovascular risk factors. Patients affected by DVT/PE were more likely to experience greater mortality, to require ICU admission, and experience prolonged ICU stays and LOH compared with COVID-19-positive patients without DVT/PE. Advancements in DVT/PE prevention are needed for patients hospitalized for COVID-19 infection.
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http://dx.doi.org/10.1016/j.jvsv.2021.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023789PMC
April 2021

Genetic basis of lacunar stroke: a pooled analysis of individual patient data and genome-wide association studies.

Lancet Neurol 2021 05 25;20(5):351-361. Epub 2021 Mar 25.

Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Background: The genetic basis of lacunar stroke is poorly understood, with a single locus on 16q24 identified to date. We sought to identify novel associations and provide mechanistic insights into the disease.

Methods: We did a pooled analysis of data from newly recruited patients with an MRI-confirmed diagnosis of lacunar stroke and existing genome-wide association studies (GWAS). Patients were recruited from hospitals in the UK as part of the UK DNA Lacunar Stroke studies 1 and 2 and from collaborators within the International Stroke Genetics Consortium. Cases and controls were stratified by ancestry and two meta-analyses were done: a European ancestry analysis, and a transethnic analysis that included all ancestry groups. We also did a multi-trait analysis of GWAS, in a joint analysis with a study of cerebral white matter hyperintensities (an aetiologically related radiological trait), to find additional genetic associations. We did a transcriptome-wide association study (TWAS) to detect genes for which expression is associated with lacunar stroke; identified significantly enriched pathways using multi-marker analysis of genomic annotation; and evaluated cardiovascular risk factors causally associated with the disease using mendelian randomisation.

Findings: Our meta-analysis comprised studies from Europe, the USA, and Australia, including 7338 cases and 254 798 controls, of which 2987 cases (matched with 29 540 controls) were confirmed using MRI. Five loci (ICA1L-WDR12-CARF-NBEAL1, ULK4, SPI1-SLC39A13-PSMC3-RAPSN, ZCCHC14, ZBTB14-EPB41L3) were found to be associated with lacunar stroke in the European or transethnic meta-analyses. A further seven loci (SLC25A44-PMF1-BGLAP, LOX-ZNF474-LOC100505841, FOXF2-FOXQ1, VTA1-GPR126, SH3PXD2A, HTRA1-ARMS2, COL4A2) were found to be associated in the multi-trait analysis with cerebral white matter hyperintensities (n=42 310). Two of the identified loci contain genes (COL4A2 and HTRA1) that are involved in monogenic lacunar stroke. The TWAS identified associations between the expression of six genes (SCL25A44, ULK4, CARF, FAM117B, ICA1L, NBEAL1) and lacunar stroke. Pathway analyses implicated disruption of the extracellular matrix, phosphatidylinositol 5 phosphate binding, and roundabout binding (false discovery rate <0·05). Mendelian randomisation analyses identified positive associations of elevated blood pressure, history of smoking, and type 2 diabetes with lacunar stroke.

Interpretation: Lacunar stroke has a substantial heritable component, with 12 loci now identified that could represent future treatment targets. These loci provide insights into lacunar stroke pathogenesis, highlighting disruption of the vascular extracellular matrix (COL4A2, LOX, SH3PXD2A, GPR126, HTRA1), pericyte differentiation (FOXF2, GPR126), TGF-β signalling (HTRA1), and myelination (ULK4, GPR126) in disease risk.

Funding: British Heart Foundation.
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http://dx.doi.org/10.1016/S1474-4422(21)00031-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062914PMC
May 2021

Treatment of migraine in patients with CADASIL: A systematic review and meta-analysis.

Neurol Clin Pract 2020 Dec;10(6):488-496

Department of Neurology (PAG, EDG, MKB, TGB, JFM), Mayo Clinic; Mayo Clinic Libraries (TJB), Mayo Clinic; and Department of Biomedical Statistics and Informatics (ERL), Mayo Clinic, Jacksonville, FL.

Background: Migraine is a common and often refractory feature for individuals with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) without consensus guidelines for treatment. Migraine treatment poses a theoretical risk within this unique population with precarious cerebrovascular autoregulation, given the vasomodulatory influence of many antimigraine medications. In this systematic review and meta-analysis, we evaluate the frequency and efficacy of treatments for migraine in individuals with CADASIL.

Methods: A search protocol was designed to include all available publications reporting antimigraine therapies for CADASIL. Individual responses to medications were categorized as unfavorable, neutral, or favorable. Responses across medication classes were compared using the Mann-Whitney test.

Results: Thirteen studies were included, yielding a cohort of 123 individuals with a median age of 53 years (range: 23-83 years), with 61% (75/123) being women. No controlled trials were identified. Simple analgesics (35.8%, 44/123) and beta-blockers (22.0%, 27/123) were the most common abortive and prophylactic strategies, respectively. Over half (54.4%) of all patients had used more than 1 medication sequentially or concomitantly. Beta-blockers were significantly associated with a neutral or unfavorable response (13.5%, 22/163, = 0.004). We found no significant associations among other medication categories.

Conclusions: Migraine in CADASIL remains a formidable therapeutic challenge, with patients often tried on several medications. Antimigraine prophylaxis with beta-blockers may be contraindicated relative to other common therapies in CADASIL. Controlled studies are needed to rigorously evaluate the safety and efficacy of antimigraine therapies in this population.
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http://dx.doi.org/10.1212/CPJ.0000000000000769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837435PMC
December 2020

Cognitive Impairment in Patients with Stroke.

Semin Neurol 2021 Feb 8;41(1):75-84. Epub 2021 Jan 8.

Department of Neurology, Mayo Clinic Florida, Jacksonville, Florida.

Despite substantial advances in stroke care, vascular cognitive impairment remains a prominent source of disability. Unlike sensorimotor impairments, cognition often continues to decline after stroke. An aging population will increase the prevalence of vascular cognitive impairment, with stroke playing an important role. Ten percent of patients presenting with stroke have pre-stroke dementia; an additional 10% will develop incident dementia with a first stroke, and 30% with a recurrent stroke. While stroke increases the risk of cognitive impairment, the presence of cognitive impairment also impacts acute stroke treatment and increases risk of poor outcome by nearly twofold. There is substantial overlap in the clinical and pathological aspects of vascular and degenerative dementias in many patients. How they relate to one another is controversial. The treatment of vascular cognitive impairment remains supportive, focusing on treating vascular risk factors. Cognitive rehabilitation after stroke is an area of active research, and existing pharmacologic treatments have limited benefit. Heightened awareness of cognitive impairment in the setting of stroke is imperative for prognostication and management, impetus for research and, ultimately, the discovery of efficacious treatments.
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http://dx.doi.org/10.1055/s-0040-1722217DOI Listing
February 2021

Cilostazol Versus Aspirin for Secondary Stroke Prevention: Systematic Review and Meta-Analysis.

J Stroke Cerebrovasc Dis 2021 Mar 31;30(3):105581. Epub 2020 Dec 31.

Department of Neurology, Mayo Clinic, Jacksonville, FL, United States.

Objectives: Cilostazol has promise as an alternative to aspirin for secondary stroke prevention given its vasodilatory and anti-inflammatory properties in addition to platelet aggregation inhibition. We aimed to conduct a systematic review and meta-analysis to estimate the efficacy and safety of cilostazol compared to aspirin for stroke prevention in patients with previous stroke or transient ischemic attack (TIA).

Materials And Methods: We searched PubMed and the Cochrane Central Register of Controlled Trials from 1996 to 2019. Randomized clinical trials that compared cilostazol to aspirin and reported the endpoints of ischemic stroke, intracranial hemorrhage and any bleeding were included. A random-effects estimate was computed based on the Mantel-Haenszel method. The pooled risk estimates with 95% confidence intervals were compared between cilostazol and aspirin.

Results: The search identified 5 randomized clinical trials comparing cilostazol vs. aspirin for secondary stroke prevention that collectively enrolled 7240 patients, all from Asian countries (3615 received cilostazol and 3625 received aspirin). Pooled results from the random-effects model showed that cilostazol was associated with significantly lower risk of recurrent ischemic stroke (RR 0.68; 95% CI, 0.54 to 0.87), intracranial hemorrhage (RR 0.42; 95% CI, 0.27 to 0.65) and any bleeding (RR 0.71; 95% CI, 0.55 to 0.91).

Conclusions: This meta-analysis suggests that cilostazol is more effective than aspirin in preventing recurrent ischemic stroke with lower risk of intracranial hemorrhage and other bleeding. Since all trials to date are from Asian countries, confirmatory trials of cilostazol for secondary stroke prevention in other populations are needed.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105581DOI Listing
March 2021

Higher Risk for Reintervention in Patients after Stenting for Radiation-Induced Internal Carotid Artery Stenosis: A Single-Center Analysis and Systematic Review.

Ann Vasc Surg 2021 May 26;73:1-14. Epub 2020 Dec 26.

Department of Neurology, Mayo Clinic, Jacksonville, FL.

Background: This study aimed to review short- and long-term outcomes of all carotid artery stenting (CAS) in patients with radiation-induced (RI) internal carotid artery (ICA) stenosis compared with patients with atherosclerotic stenosis (AS).

Methods: We performed a single-center, multisite case-control study of transfemoral carotid artery intervention in patients stented for RI or AS. Cases of stented RI carotid arteries were identified using a CAS database covering January 2000 to December 2019. These patients were randomly matched 2:1 with stented patients because of AS by age, sex, and year of CAS. A conditional logistic regression model was performed to estimate the odds of reintervention in the RI group. Finally, a systematic review was performed to assess the outcomes of RI stenosis treated with CAS.

Results: There were 120 CAS in 113 patients because of RI ICA stenosis. Eighty-nine patients (78.8%) were male, and 68 patients (60.2%) were symptomatic. The reasons for radiation included most commonly treatment for diverse malignancies of the head and neck in 109 patients (96.5%). The mean radiation dose was 58.9 ± 15.6 Gy, and the time from radiation to CAS was 175.3 ± 140.4 months. Symptoms included 31 transient ischemic attacks (TIAs), 21 strokes (7 acute and 14 subacute), and 17 amaurosis fugax. The mean National Institutes of Health Stroke Scale in acute strokes was 8.7 ± 11.2. In asymptomatic patients, the indication for CAS was high-grade stenosis determined by duplex ultrasound. All CAS were successfully completed. Reinterventions were more frequent in the RI ICA stenosis cohort compared with the AS cohort (10.1% vs. 1.4%). Reinterventions occurred in 14 vessels, and causes for reintervention were restenosis in 12 followed by TIA/stroke in two vessels. On conditional regression modeling, patients with RI ICA stenosis were at a higher risk for reintervention (odds ratio = 7.1, 95% confidence interval = 2.1-32.8; P = 0.004). The mean follow-up was 33.7 ± 36.9 months, and the mortality across groups was no different (P = 0.12).

Conclusions: In our single-center, multisite cohort study, patients who underwent CAS for RI ICA stenosis experienced a higher rate of restenosis and a higher number of reinterventions compared with CAS for AS. Although CAS is safe and effective for this RI ICA stenosis cohort, further data are needed to reduce the risk of restenosis, and close patient surveillance is warranted. In our systematic review, CAS was considered an excellent alternative option for the treatment of patients with RI ICA stenosis. However, careful patient selection is warranted because of the increased risk of restenosis on long-term follow-up.
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http://dx.doi.org/10.1016/j.avsg.2020.11.027DOI Listing
May 2021

Carotid Artery Stenosis in a Young Asymptomatic Patient: The Value of Multimodal Cross-Sectional Imaging.

Neurology 2021 02 22;96(7):342. Epub 2020 Dec 22.

From the Division of Vascular and Endovascular Surgery (C.F.-M., Y.E.) and Departments of Neurology (M.L., J.F.H., J.L.S., J.F.M.), Radiology (S.S.S.), Critical Care Medicine (J.L.S.), Neurosurgery (J.L.S.), and Laboratory Medicine and Pathology (A.N.), Mayo Clinic Florida, Jacksonville.

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http://dx.doi.org/10.1212/WNL.0000000000011417DOI Listing
February 2021

Telemedicine in vascular surgery during the coronavirus disease-2019 pandemic: A multisite healthcare system experience.

J Vasc Surg 2021 07 16;74(1):1-4. Epub 2020 Dec 16.

Center for Connected Care, Mayo Clinic, Jacksonville, Fla; Division of Plastic and Reconstructive Surgery, Mayo Clinic, Jacksonville, Fla.

Objective: To assess the introduction of telemedicine as an alternative to the traditional face-to-face encounters with vascular surgery patients in the era of the coronavirus disease 2019 (COVID-19) pandemic.

Methods: A retrospective review of prospectively collected data on face-to-face and telemedicine interactions was conducted at a multisite health care system from January to August 2020 in vascular surgery patients during the COVID-19 pandemic. The end point is direct patient satisfaction comparison between face-to-face and telemedicine encounters/interactions prior and during the pandemic.

Results: There were 6262 patient encounters from January 1, 2020, to August 6, 2020. Of the total encounters, 790 (12.6%) were via telemedicine, which were initiated on March 11, 2020, after the World Health Organization's declaration of the COVID-19 pandemic. These telemedicine encounters were readily adopted and embraced by both the providers and patients and remain popular as an option to patients for all types of visits. Of these patients, 78.7% rated their overall health care experience during face-to-face encounters as very good and 80.6% of patients rated their health care experience during telemedicine encounters as very good (P = .78).

Conclusions: Although the COVID-19 pandemic has produced unprecedented consequences to the practice of medicine and specifically of vascular surgery, our multisite health care system has been able to swiftly adapt and adopt telemedicine technologies for the care of our complex patients. Most important, the high quality of patient-reported satisfaction and health care experience has remained unchanged.
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http://dx.doi.org/10.1016/j.jvs.2020.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738278PMC
July 2021

Prevalence of Intracranial Aneurysms in Patients with Infrarenal Abdominal Aortic Aneurysms: A Multicenter Experience.

Int J Angiol 2020 Dec 27;29(4):229-236. Epub 2020 Jun 27.

Department of Neurology, Mayo Clinic, Jacksonville, Florida.

Prior studies suggest high prevalence of intracranial aneurysms (IA) in patients with infrarenal abdominal aortic aneurysms (AAA). We reviewed our multicenter experience in clinical detection/treatment of IAs in AAA patients and estimated the risk of IA in patients with AAA relative to patients without AAA. We reviewed cases of vascular surgery infrarenal AAA repairs at three Mayo Clinic sites from January 1998 to December 2018. Concurrent controls were randomly matched in a 1:1 ratio by age, sex, smoking history, and head imaging characteristics. Conditional logistic regression was used to calculate odds ratios. We reviewed 2,300 infrarenal AAA repairs. Mean size of AAA at repair was 56.9 ± 11.4 mm; mean age at repair, 75.8 ± 8.0 years. 87.5% of the cases (  = 2014) were men. Head imaging was available in 421 patients. Thirty-seven patients were found to have 45 IAs for a prevalence of 8.8%. Mean size of IA was 4.6 ± 3.5 mm; mean age at IA detection, 72.0 ± 10.8 years. Thirty (81%) out of 37 patients were men. Six patients underwent treatment for IA: four for ruptured IAs and two for unruptured IAs. All were diagnosed before AAA repair. Treatment included five clippings and one coil-assisted stenting. Time from IA diagnosis to AAA repair was 16.4 ± 11.0 years. Two of these patients presented with ruptured AAA, one with successful repair and a second one that resulted in death. Odds of IA were higher for patients with AAA versus those without AAA (8.8% [37/421] vs. 3.1% [13/421]; OR 3.18; 95% confidence interval, 1.62-6.27,  < 0.001). Co-prevalence of IA among patients with AAA was 8.8% and is more than three times the rate seen in patients without AAA. All IAs were diagnosed prior to AAA repair. Surveillance for AAA after IA treatment could have prevented two AAA ruptures and one death.
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http://dx.doi.org/10.1055/s-0040-1713139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690990PMC
December 2020

Plasma neurofilament light predicts mortality in patients with stroke.

Sci Transl Med 2020 11;12(569)

Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

Given the heterogeneity of stroke brain injury, there is a clear need for a biomarker that determines the degree of neuroaxonal injury across stroke types. We evaluated whether blood neurofilament light (NFL) would fulfill this purpose for patients with acute cerebral infarction (ACI; = 227), aneurysmal subarachnoid hemorrhage (aSAH; = 58), or nontraumatic intracerebral hemorrhage (ICH; = 29). We additionally validated our findings in two independent cohorts of patients with ICH ( = 96 and = 54) given the scarcity of blood biomarker studies for this deadliest stroke type. Compared to healthy individuals ( = 79 and = 48 for the discovery and validation cohorts, respectively), NFL was higher for all stroke types. NFL associated with radiographic markers of brain tissue damage. It correlated with the extent of early ischemic injury in patients with ACI, hemorrhage severity in patients with aSAH, and intracranial hemorrhage volume in patients with ICH. In all patients, NFL independently correlated with scores from the NIH Stroke Scale, the modified Rankin Scale, and the Mini-Mental State Examination at blood draw, which respectively assess neurological, functional, and cognitive status. Furthermore, higher NFL concentrations independently associated with 3- or 6-month functional disability and higher all-cause mortality. These data support NFL as a uniform method to estimate neuroaxonal injury and forecast mortality regardless of stroke mechanism. As a prognostic biomarker, blood NFL has the potential to assist with planning supportive and rehabilitation services and improving clinical trial efficiency for stroke therapeutics and devices.
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http://dx.doi.org/10.1126/scitranslmed.aay1913DOI Listing
November 2020

Mitigating the effects of COVID-19 pandemic on controlling vascular risk factors among participants in a carotid stenosis trial.

J Stroke Cerebrovasc Dis 2020 Dec 30;29(12):105362. Epub 2020 Sep 30.

Neurology, Mayo Clinic, Jacksonville, FL, United States.

Introduction: The COVID-19 pandemic has presented challenges to managing vascular risk factors with in-person follow-up of patients with asymptomatic carotid stenosis enrolled in the CREST2 trial. CREST2 is comparing intensive medical management alone versus intensive medical management plus revascularization with endarterectomy or stenting. We performed a study to evaluate the feasibility of a home-based program for testing blood pressure (BP) and low-density lipoprotein (LDL) in CREST2.

Methods: This study involved 45 patients at 10 sites in the CREST2 trial. The initial patients were identified by the Medical Management Core (MMC) as high-risk patients defined by stage 2 hypertension, LDL > 90 mg/dl, or both. If a patient at the site declined participation, another was substituted. All patients who agreed to participate were sent a BP monitoring device and a commercially available at-home lipid test kit that uses a self-performed finger-stick blood sample that was resulted to the patient. Training on the use of the equipment and obtaining the risk factor results was done by the study coordinator by telephone.

Results: Ten of the 130 currently active CREST2 sites participated, 8 in the LDL portion and 5 in the BP portion (3 sites did both). Twenty-six BP devices and 23 lipid tests were sent to patients. Of the 26 patients who obtained BP readings with the devices, 9 were out of the study target and adjustments in BP medications were made in 3. Of the 23 patients sent LDL tests, 13 were able to perform the test showing 7 were out of target, leading to adjustments in lipid medications in 4.

Conclusion: This study established the feasibility of at-home monitoring of BP and LDL in a clinical trial and identified implementation challenges prior to widespread use in the trial. (ClinicalTrials.gov number NCT02089217).
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524666PMC
December 2020

Predicting Who Will Experience Cerebral Hemorrhage When Anticoagulated.

Authors:
James F Meschia

Mayo Clin Proc 2020 10;95(10):2057-2059

Department of Neurology, Mayo Clinic, Jacksonville, FL. Electronic address:

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http://dx.doi.org/10.1016/j.mayocp.2020.08.025DOI Listing
October 2020

Rationale, Design, and Implementation of Intensive Risk Factor Treatment in the CREST2 Trial.

Stroke 2020 10 21;51(10):2960-2971. Epub 2020 Sep 21.

Neurology, Mayo Clinic, Jacksonville, FL (J.F.M., T.G.B.).

Background And Purpose: The CREST2 trial (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis) is comparing intensive medical management (IMM) alone to IMM plus revascularization with carotid endarterectomy or transfemoral carotid artery stenting for preventing stroke or death within 44 days after randomization or ipsilateral ischemic stroke thereafter. There are extensive clinical trial data on outcomes after revascularization of asymptomatic carotid stenosis, but not for IMM. As such, the experimental treatment in CREST2 is IMM, which is described in this article.

Methods: IMM consists of aspirin 325 mg/day and intensive risk factor management, primarily targeting systolic blood pressure <130 mm Hg (initially systolic blood pressure <140 mm Hg) and LDL (low-density lipoprotein) cholesterol <70 mg/dL. Secondary risk factor targets focus on tobacco smoking, non-HDL (high-density lipoprotein), HbA1c (hemoglobin A1c), physical activity, and weight. Risk factor management is performed by site personnel and a lifestyle coaching program delivered by telephone. We report interim risk factor data on 1618 patients at baseline and last follow-up through 24 months.

Results: The mean baseline LDL of 80.5 mg/dL improved to 66.7 mg/dL. The mean baseline systolic blood pressure of 139.7 mm Hg improved to 130.3 mm Hg. The proportion of patients in-target improved from 43% to 61% for systolic blood pressure <130 mm Hg and from 45% to 67% for LDL<70 mg/dL (both changes <0.001).

Conclusions: The rigorous multimodal approach to intensive stroke risk factor management in CREST2 has resulted in significant improvements in risk factor control that will enable a comparison of cutting-edge medical care to revascularization in patients with asymptomatic carotid stenosis. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02089217.
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http://dx.doi.org/10.1161/STROKEAHA.120.030730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530035PMC
October 2020

Safety, Tolerability, and Efficacy of Pain Reduction by Gabapentin for Acute Headache and Meningismus After Aneurysmal Subarachnoid Hemorrhage: A Pilot Study.

Front Neurol 2020 28;11:744. Epub 2020 Jul 28.

Department of Neurology, Mayo Clinic, Jacksonville, FL, United States.

Severe, often sudden-onset headache is the principal presenting symptoms of aneurysmal subarachnoid hemorrhage (aSAH). We hypothesized that gabapentin would be safe and tolerable for aSAH-induced headaches and would reduce concurrent opioid use. We performed a single-center, double-blind, randomized, placebo-controlled trial (registered at ClinicalTrials.gov; NCT02330094) from November 24, 2014, to June 24, 2017, where aSAH patients received either dose-escalating gabapentin or oral placebo, both alongside a standard of care pain regimen. After 7 days, patients had the option to continue in an open-label period until 14 days after enrollment or until discharge from the intensive care unit. Our primary endpoint was the efficacy of gabapentin in reducing headache numeric pain scores and opioid usage in patients with aSAH compared to the placebo group. We identified 63 potential patients with aSAH for the study. After applying stringent exclusion criteria, 16 eligible patients were enrolled into one of two arms. The study ended prematurely after reaching a pre-specified funding period and an unexpected drop in aSAH cases. There was a trend toward lower headache numeric pain scores and opioid use in the gabapentin treated arm; however this was not significantly different. Gabapentin was well tolerated by participants and no adverse effects were reported. While there was a trend toward lower pain scores and opioid requirement in the gabapentin group, the study was underpowered to detect a difference. Larger multicenter trials are required to evaluate the efficacy of gabapentin to reduce opioid requirements after aSAH.
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http://dx.doi.org/10.3389/fneur.2020.00744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399216PMC
July 2020

Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke.

Stroke 2020 08 22;51(8):2454-2463. Epub 2020 Jul 22.

Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC (C.D.L., C.L.).

Background And Purpose: Stroke is a complex disease with multiple genetic and environmental risk factors. Blacks endure a nearly 2-fold greater risk of stroke and are 2× to 3× more likely to die from stroke than European Americans.

Methods: The COMPASS (Consortium of Minority Population Genome-Wide Association Studies of Stroke) has conducted a genome-wide association meta-analysis of stroke in >22 000 individuals of African ancestry (3734 cases, 18 317 controls) from 13 cohorts.

Results: In meta-analyses, we identified one single nucleotide polymorphism (rs55931441) near the gene that reached genome-wide significance (=4.62×10) and an additional 29 variants with suggestive evidence of association (<1×10), representing 24 unique loci. For validation, a look-up analysis for a 100 kb region flanking the COMPASS single nucleotide polymorphism was performed in SiGN (Stroke Genetics Network) Europeans, SiGN Hispanics, and METASTROKE (Europeans). Using a stringent Bonferroni correction value of 2.08×10 (0.05/24 unique loci), we were able to validate associations at the locus in both SiGN (=8.18×10) and METASTROKE (=1.72×10) European populations. Overall, 16 of 24 loci showed evidence for validation across multiple populations. Previous studies have reported associations between variants in the gene and lipids, C-reactive protein, and risk of coronary artery disease and stroke. Suggestive associations with variants in the and genes represent potential novel ischemic stroke loci.

Conclusions: These findings represent the most thorough investigation of genetic determinants of stroke in individuals of African descent, to date.
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http://dx.doi.org/10.1161/STROKEAHA.120.029123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387190PMC
August 2020
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